The major purpose of this study is to determine mechanisms of action of drugs and diets used in treatment of hyperlipoproteinemia. An understanding of these mechanisms is important for determining whether reduction of plasma lipoproteins occurs through beneficial or harmful mechanisms. In studies of the effects of unsaturated dietary fats, it was shown that these fats lower plasma cholesterol in parallel with reduction of plasma triglycerides and it seems likely that cholesterol reduction is the consequence of alterations in triglyceride metabolism. In patients with hypertriglyceridemia, cholesterol lowering by unsaturated fats is accompanied by an increased excretion of cholesterol and/or bile acids. Thus, reduction of plasma cholesterol seems to be associated with a decrease in total body cholesterol. In addition to the type of dietary fat, we have shown that the quantity of calories in the diet influences the synthesis of both cholesterol and bile acids. In obese patients, the synthesis of both cholesterol and bile acids are reduced by decreased intake of calories, and when food is withheld, bile acid synthesis is markedly inhibited despite the interruption of the enterohepatic circulation of bile acids. These studies show that the fat and calorie content of the diet are vital for the regulation of cholesterol metabolism.